We have shown that rhesus monkeys with multiple inoculations of Brugia malayi L3 develop lymphatic pathology and immune responses that resemble, in many aspects, those of filarial patients. One of the similarities of the immune response is that both exhibit T-cell unresponsiveness to B. malayi adult antigen (BmA) in vitro. In the present study reverse transcriptase polymerase chain reaction (RT-PCR) assays were employed to investigate IL-2, IFN- , IL-l0, IL-4 and TNF-alpha cytokine mRNA expression in peripheral blood mononuclear cells (PBMC) from infected monkeys stimulated in vitro with BmA. We also correlated cytokine-mRNA expression with lymphedema, microfilaremia and in vitro blastogenesis to BmA. Nine Brugia-infected monkeys were divided according to the ability of their PBMC to proliferate in vitro to BmA. Three of these were classified as responder monkeys (RM) (S.I. >2) and 6 as nonresponders (NRM) (S.I.<2). All 3 RM had lymphedema and only one was microfilaremic. On the other hand, none of the 6 NRM developed lymphedema and 5 of them were microfilaremic. When cytokine-mRNA expression was investigated, IL-2 and lFN- transcripts were induced in cells from 2 out of 3 and all 3 RM, respectively. On the contrary, cells from only 1 out of 6 and 2 out of 6 NRM showed induction of IL-2 and lFN-transcripts, respectively. IL-10 mRNA expression was induced in cells from 5 out of 6 NRM and in 2 out of 3 RM. IL-4 mRNA was induced in all the NRM and in 2 out of 3 RM. Cells from all the infected monkeys showed high levels of TNF-alpha mRNA expression. These results suggest that there is an imbalance in the Th1 and Th2 cytokine patterns in infected rhesus monkeys, and that the lack of expression of Th1 cytokines could be the cause of the unresponsiveness of PBMC from Brugian rhesus monkeys to BmA.